Abstract
ABSTRACTNeisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions differing in nutrient supply, like the nasopharynx, blood, and cerebrospinal fluid, by changing metabolism and protein repertoire. However, regulatory transcription factors and two-component systems in meningococci involved in adaptation to local nutrient variations are limited. We identified novel sibling small regulatory RNAs (Neisseria metabolic switch regulators [NmsRs]) regulating switches between cataplerotic and anaplerotic metabolism in this pathogen. Overexpression of NmsRs was tolerated in blood but not in cerebrospinal fluid. Expression of six tricarboxylic acid cycle enzymes was downregulated by direct action of NmsRs. Expression of the NmsRs themselves was under the control of the stringent response through the action of RelA. Small sibling regulatory RNAs of meningococci, controlling general metabolic switches, add an exciting twist to their versatile repertoire in bacterial pathogens.
Highlights
Neisseria meningitidis is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis
We identified two highly conserved small regulatory RNAs (sRNAs), designated sibling Neisseria metabolic switch regulators (NmsRs), in N. meningitidis which are functionally involved in the regulation of tricarboxylic acid (TCA) cycle activity by antisense mechanisms
In whole-transcriptome analysis (WTA) of meningococci grown in nutrient-rich culture medium, we identified two structurally nearly identical sRNAs with 70% sequence identity, tandemly arranged in N. meningitidis strain H44/76 (Fig. 1) [15]
Summary
Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. IMPORTANCE Regulatory small RNAs (sRNAs) of pathogens are coming to be recognized as highly important components of riboregulatory networks, involved in the control of essential cellular processes They play a prominent role in adaptation to physiological changes as represented by different host environments. We identified highly conserved sibling sRNAs in Neisseria meningitidis which are functionally involved in the regulation of gene expression of components of the tricarboxylic acid cycle These novel sibling sRNAs that function by antisense mechanisms extend the so-called stringent response which connects metabolic status to colonization and possibly virulence as well as pathogenesis in meningococci. SRNAs are important players in many cellular processes and prominent in those involving adaptive physiological changes They can function as posttranscriptional regulators of gene expression to orchestrate stress responses and metabolism. The RNA chaperonin protein Hfq is frequently involved, enhancing these processes [13, 14]
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